Method for preparing 4-hydroquinolines and/or tautomeric compounds

ABSTRACT

The invention concerns a method for preparing 4-hydroquinolines and/or tautomeric compounds. More particularly, the invention concerns 5,7-dichloro-4-quinolines and/or its tautomeric compounds. The method is characterized in that it consists in heating a 4-hydroquinolinecarboxylic acid, its derivatives or precursors, at a temperature not more than 200° C. in the presence of a base.

This application is an application under 35 U.S.C. Section 371 ofInternational Application Number PCT/FR99/02985 filed on Dec. 1, 1999.

The present invention relates to a process for preparing4-hydroxyquinolines and/or their tautomeric forms. More particularly,the invention relates to 5,7-dichloro-4-hydroxyquinoline and/or itstautomeric forms.

5,7-dichloro-4-hydroxyquinoline (DCHQ) is an intermediate used in theplant protection field.

The industrial scale preparation of such a product is a problem, andexisting processes are in need of refining.

C. C. Price et al. (Organic Synthesis 3, p. 272) disclose thepreparation of 4-hydroxyquinolines using a process consisting ofdecarboxylation of 4-hydroxy-3-quinolinecarboxylic acids that have beenobtained by alkaline or acid hydrolysis of the corresponding esters.However, decarboxylation is carried out at a high temperature of morethan 230° C.

U.S. Pat. No. 5,731,440 proposes improving that process by carrying outthe decarboxylation step at a lower temperature in the range 120° C. to165° C., but uses a strong acid medium such as sulphuric acid,phosphoric acid or hydrochloric acid. The disadvantage of that processis that the medium is highly corrosive because of the presence of astrong acid.

The Applicant has discovered an improved hydroxyquinoline preparationprocess.

The process of the invention is characterized in that a4-hydroxyquinolinecarboxylic acid, a derivative or precursor thereof, isheated to a temperature of at most 200° C. in the presence of a base.

It has unexpectedly been discovered that it is possible to carry outdecarboxylation of 4-hydroxyquinolinecarboxylic acids and esters thereofat a low temperature, advantageously in the range 90° C. to 160° C., ingood reaction yields. This is of enormous advantage from an industrialviewpoint.

The process of the invention uses a quinolinic compound.

The term “quinolinic compound” means a heterocyclic compound comprisinga quinoline moiety. This term is also used for naphthpyridine typecompounds that are also included in the scope of the process of theinvention.

The heterocycle of the quinolinic compound carries at least one hydroxylgroup in the 4-position and a functional group in the position α to thehydroxyl group. Other substituents can also be present in particular inthe 5- and/or 7-position.

Regarding the nature of the functional group that is shown in formula(I) below by the symbol Y, this is a carboxylic group (COOH), aprecursor group (nitrile) or a derivative group (ester or amide).

The starting quinolinic compound of the invention can be represented bythe following general formula:

in which formula (I):

R₁, which may be identical or different, represents:

a linear or branched alkyl group containing 1 to 12 carbon atoms,preferably 1 to 4 carbon atoms, such as methyl, ethyl, propyl,isopropyl, butyl, isobutyl, sec-butyl, tert-butyl;

a linear or branched alkyl group carrying one or more halogen atoms,containing 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms, such asmethyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl,tert-butyl;

a linear or branched alkenyl group containing 2 to 12 carbon atoms,preferably 2 to 4 carbon atoms, such as vinyl or allyl,

a cyclohexyl, phenyl or benzyl group;

a linear or branched alkoxy or thioether group containing 1 to 6 carbonatoms, preferably 1 to 4 carbon atoms, such as a methoxy, ethoxy,propoxy, isopropoxy or butoxy radical;

an acyl group containing 2 to 6 carbon atoms;

a nitro group;

an amino group, optionally substituted by alkyl groups containing 1 to 6carbon atoms;

a halogen atom, preferably a chlorine or bromine atom;

a trifluoromethyl group;

an alkenylene group containing 3 or 4 carbon atoms that can form a ringwith the carbon atoms adjacent to the phenyl ring;

Y represents one of the following groups:

a CN group;

a COOR₂ group;

a CONR₃R₄ group;

in which groups R₂, R₃ or R₄, which may be identical or different,represent a hydrogen atom or an alkyl, cyclohexyl, phenyl or benzylgroup;

n is a number in the range 1 to 4, preferably 1 or 2.

Particularly suitable substituents in the 5- and/or 7-position arehalogen atoms such as fluorine, chlorine, bromine, iodine or a —CF₃ typegroup.

Preferred non-limiting illustrative examples from the list ofsubstituents are the chlorine atom, methyl radical and methoxy radical.

The nature of R₂, R₃ and R₄ is not critical provided that thecarboxylate group is eliminated. For reasons of economy, it is usually alinear or branched alkyl group containing 1 to 6 carbon atoms,preferably 1 to 4 carbon atoms, but it is possible to use other groups,for example cyclohexyl, phenyl or benzyl groups, or any other group.

More particular compounds with formula (I) for use in the process of theinvention that can be cited are4-hydroxy-5,7-dichloroquinoline-3-carboxylic acid, and methyl or ethyl4-hydroxy-5,7-dichloroquinoline-3-carboxylate.

The starting quinolinic compounds with formula (I) are known productsthat can in particular be obtained by reacting substituted anilines withalkyl alkoxymethylenemalonates (cf. C. C. Price et al., OrganicSynthesis 3, p. 272).

It should be noted that the invention is applicable to quinoliniccompounds with formula (I) and also to tautomeric forms that can berepresented by formula (II):

in which formula (II), R₁, Y and n have the meanings given above forformula (I).

In accordance with the process of the invention, the quinolinic compoundis decarboxylated in the presence of a base.

A mineral or organic base can be used in the process of the invention.

Preferably, a sufficiently strong base is selected, i.e., a base with anassociated acid the pKa of which is more than 5 or close to 5: the pKais defined as the cologarithm of the dissociation constant of the acid,in an aqueous medium, at 25° C.

Particularly suitable bases for carrying out the process of theinvention that can be cited are alkaline bases derived from alkalimetals or alkaline-earth metals.

The term “alkali metals” as used in the present text means elements fromcolumn 1A of the periodic table, preferably alkali metals such aslithium, sodium, potassium, rubidium and caesium.

The term “alkaline-earth metal” as used in the present text meanselements from column 2A of the periodic table, preferably alkaline-earthmetals such as beryllium, magnesium, calcium, strontium and barium.

For a definition of the elements, reference should be made to theperiodic table published in the “Bulletin de la Société Chimique deFrance”, N^(o) 1, (1966).

The process of the invention preferably employs an alkali metalhydroxide, preferably potassium hydroxide or sodium hydroxide, or analkali metal bicarbonate or carbonate, preferably potassium or sodiumbicarbonate or carbonate.

It is also possible to use a quaternary ammonium hydroxide.

Examples of quaternary ammonium hydroxides that are preferably used aretetraalkylammonium or trialkylbenzylammonium hydroxides wherein thealkyl radicals, which may be identical or different, represent a linearor branched alkyl chain containing 1 to 12 carbon atoms, preferably 1 to6 carbon atoms.

Preferably, tetramethylammonium hydroxide, tetraethylammonium hydroxideor tetrabutylammonium hydroxide are used.

It is also possible to use trialkylbenzylammonium hydroxides, inparticular trimethylbenzylammonium hydroxide.

The process of the invention can also employ monofunctional orbifunctional primary, secondary or tertiary aliphatic, carbocyclic orheterocyclic, aromatic or non aromatic amines.

More specific examples that can be mentioned are tri-n-butylamine,di-n-butylamine, hexamethylenediamine, cyclohexylamine,N-methylpyrrolidine, 4-dimethylaminopyridine, morpholine, quinoline,pyridine, 3-picoline and 5-picoline.

From an economic and practical viewpoint, the base that is selected ispreferably potassium or sodium hydroxide.

The base is advantageously used in the form of an aqueous solution.

The concentration of the basic solution is preferably in the range 2% to45% by weight, more preferably in the range 5% to 30%.

The quantity of based used, expressed as the mole ratio between thenumber of moles of base (or equivalents of base) and the number of molesof quinolinic compound, is preferably in the range 1 to 6, morepreferably in the range 1.5 to 3.5.

The decarboxylation reaction carried out in the process of the inventionis preferably carried out in the presence of water, which can be in theliquid and/or vapour form.

The quantity of quinolinic compound used preferably represents 2% to50%, more preferably 5% to 35% by weight of the weight of the water.

Preferably, the water is supplied by the basic solution.

The process of the invention can be implemented in a number of ways.

In a first variation, decarboxylation is carried out by heating thereaction mixture including the quinolinic compound, the base and water.

In a second variation, the quinolinic compound and the base are mixed inaqueous solution, the water is evaporated off then the decarboxylationreaction is effected by heating in a completely solid medium.

Finally, in a third variation of the process of the invention, anorganic solvent that may or may not be miscible with water is added to areaction medium including the quinolinic compound, base, and water.

The organic solvent does not have to dissolve the quinolinic compound.

Preferably, an organic solvent is selected that is not miscible withwater and has a high boiling point.

A preferred solvent for this type of reaction is a eutectic mixture ofbiphenyl oxide and biphenyl sold under the trade names of THERMINOL VP1,DOWTHERM or GILOTHERM DO. When used, the decarboxylation temperature isadvantageously selected so as to be in the preferred temperature zone.

It is also possible to use other solvents such as triphenylmethane,sulpholane, benzylbenzene, 1,4-dibenzylbenzene, a silicone oil orpetroleum cuts with a high boiling point of more than the selectedreaction temperature.

Organic solvents such as dimethylformamide or N,N′-diacetamide are alsosuitable.

An alcohol type solvent is also suitable, more particularly propanol,isopropanol or n-butanol.

The concentration of quinolinic compound in the organic solvent is suchthat the weight ratio between the organic solvent and the quinoliniccompound is preferably in the range 1 to 30, more preferably in therange 1 to 10.

If the base used is liquid, for example an amine, it is also possible toimplement a further variation which consists of carrying outdecarboxylation by heating the reaction mixture comprising thequinolinic compound and a base, in the absence of water.

Thus, depending on the implementations of the invention, the medium canbe liquid, solid or two-phase (liquid/liquid or liquid/solid) or eventhree-phase (liquid/liquid/solid). Thus the choice of reactor will beadapted as a consequence.

The reaction is carried out under autogenous pressure.

Regarding the decarboxylation operation proper, it is carried out byheating the reaction medium. The decarboxylation temperature is at most200° C., preferably in the range 90° C. to 190° C., and more preferablyin the range 95° C. to 180° C.

The heating period must be sufficient for the reaction to be completedto a sufficient degree.

It should be noted that the process is of particular importance whenusing a quinolinic compound in the form of an ester, as because of thepresence of the base, ester hydrolysis occurs during the decarboxylationstep, simultaneously and/or successively.

At the end of the operation, depending on the quantity of base used, aproduct is obtained in the free (acid) form or salt form thatessentially comprises the desired quinolinic compound (B) in equilibriumwith its tautomeric form (A), with the following formulae:

where R₁ and n have the meanings given above and M represents a hydrogenatom or the cation of the base introduced initially. This cation ispreferably an alkali metal if the base used initially is an alkali metalhydroxide, as indicated above.

At the end of the reaction, the reaction medium is treatedconventionally.

Thus, when the organic phase is present and when the base is used inexcess, the product obtained is in the form of the salt in the aqueousphase which is separated from the organic phase, for example bydecanting.

When the base is in excess, acid treatment is carried out to recover thedesired free product in the form of a precipitate.

To this end, an acid is added, preferably hydrochloric acid, sulphuricacid or phosphoric acid, in a quantity such that the 4-hydroxyquinolineproduced is in the free form.

The concentration of the starting acid is anywhere in the range 10% to90% by weight of acid, but preferably, a dilute acid solution is used,preferably 20% to 50% by weight.

The precipitate is separated using conventional solid-liquid separationtechniques, preferably by filtering.

Washing the precipitate to eliminate traces of organic liquid may bedesirable. To this end, water or a solvent with a low boiling point canbe used, for example less than 150° C., preferably in the range 60° C.to 120° C. Particular examples of eminently suitable solvents are:o-dichlorobenzene, methylcyclohexane, benzene, toluene, chlorobenzene,methanol and ethanol.

The decarboxylated product is obtained in a very high yield.

When the base is not used in excess, acid does not need to be added. Thefree quinolinic compound is obtained directly in the form of aprecipitate which only needs separation, for example by filtering.

The filtrate which contains the base is optionally recycled to otherdecarboxylation operations.

The invention is particularly suitable for the preparation of a4-hydroxy-7-halogenoquinolines, preferably 4-hydroxy-7-chloroquinolineand its isomer, or a 4-hydroxy-5-halogenoquinoline, preferably4-hydroxy-5-chloroquinoline. It is eminently suitable for preparing5,7-dichloro-4-hydroxyquinoline.

Examples will now be given which illustrate the invention without in anyway limiting its scope.

In the examples, the percentages are given by weight.

The abbreviations have the following meanings:

DCHQ=5,7-dichloro-4-hydroxyquinoline;

ODCQA=4-hydroxy-5,7-dichloroquinoline-3-carboxylic acid;

The degree of transformation (TT) corresponds to the ratio between thenumber of moles of substrate transformed and the number of moles ofsubstrate engaged;

The yield (RR) corresponds to the ratio between the number of moles ofproduct formed and the number of moles of substrate engaged.

EXAMPLE 1

1.55 g (6 mmoles) of 4-hydroxy-5,7-dichloroquinoline-3-carboxylic acid(ODCQA) and 5.6 g of an aqueous 12% potassium hydroxide solution (12mmoles of KOH) were charged into an autoclave, then it was stirred at150° C.

After reacting for 5 hours, high performance liquid chromatographicanalysis was carried out:

degree of transformation (TT) of ODCQA>99%;

DCHQ yield=99%.

EXAMPLES 2 TO 13

The same procedure as that used in Example 1 was used, changing certainparameters; in particular, an organic solvent was used in Examples 7 to10, namely therminol VP1, a eutectic mixture of biphenyl and biphenyloxide.

The results obtained are shown in Table (I).

TABLE (I) KOH/ TT RR Ref. ODCQA [KOH] Time ODCQA DCHQ Ex. mole ratio %Solvent T° C. h % % 2 1.8 25 None 95 63 37 36 3 2 25 None 95 63 43 51 42.2 25 None 95 63 49 48 5 4 30 None 95 15 — 11 6 4 25 None 105 15 8 9 71.5 25 Therminol VP1 110 15 44 30 8 2 25 Therminol VP1 110 15 62 57 92.5 25 Therminol VP1 110 15 74 70 10 2 25 Therminol VP1 120 15 89 63 112.5 12 None 150 5 >99 93 12 3 12 None 150 5 98 67 13 4.5 12 None 150 556 56

EXAMPLE 14

The procedure of the above examples was followed, operating in theabsence of an organic solvent, with a KOH/ODCQA mole ratio of 2: thewater present was supplied by the KOH solution.

The results obtained are shown in the following table:

TABLE (II) KOH/ [KOH] TT RR Ref. ODCQA mol/kg of Time ODCQA DCHQ Ex.mole ratio reaction medium Solvent T° C. h % % 14 2 1.35 None 140 5 99.497

EXAMPLE 15

1.55 g (6 mmoles) of 4-hydroxy-5,7-dichloroquinoline-3-carboxylic acid(ODCQA) and 9.8 g of an aqueous 12% potassium hydroxide solution (21mmoles of KOH) were charged into an autoclave, then it was stirred at150° C.

After reacting for 5 hours, high performance liquid chromatographicanalysis was carried out on a sample that had been removed.

The following results were obtained:

degree of transformation (TT) of ODCQA=77%;

DCHQ yield=77%.

11.56 g of an aqueous 10% sulphuric acid solution (11.9 mmoles) wasadded to the crude mixture (10.45 g, corresponding to 92% of the totalinitial mass) remaining after removing the sample for analysis.

The reaction mixture was stirred at 70° C. for 50 min, and theprecipitate obtained was washed with water then dried under reducedpressure (10 mm of mercury) at 70° C.

1.24 g of product was obtained.

High performance liquid chromatography of this product showed that itcontained 75% of DCHQ and 25% of ODCQA.

EXAMPLE 16

1.72 g (6 mmoles) of ethyl 4-hydroxy-5,7-dichloroquinoline-3-carboxylate(ODCQE), 2.69 g of an aqueous 25% potassium hydroxide solution (12mmoles of KOH) and 6.45 g of Therminol VP1 were charged into anautoclave and heated to 150° C. with stirring.

After reacting for 15 hours, high performance liquid chromatographyanalysis was carried out with a slightly acidic eluent:

degree of transformation (TT) of ODCQE>99%;

degree of transformation (TT) of ODCQA>99%;

DCHQ yield=86%.

EXAMPLES 17 TO 22

The same procedure as that used for Example 16 was used, changingcertain parameters.

The results obtained are shown in Table (III).

TABLE (III) KOH/ TT TT RR Ref. ODCQA [KOH] Time ODCQE ODCQA DCHQ Ex.mole ratio % Solvent T° C. h % % % 17 2 25 Therminol VP1 95 63 100 61 5518 2 25 Therminol VP1 110 15 100 43 39 19 2.5 25 Therminol VP1 110 15100 71 65 20 1.5 25 Therminol VP1 110 15 100 39 26 21 2 25 DMAC 120 15100 51 21 22 2.5 25 Therminol VP1 120 15 100 95 84

EXAMPLE 23

a—Preparation of ethyl 4-hydroxy-5,7-dichloroquinoline-3-carboxylate

266 ml of Therminol VP1, 56.8 g (0.263 mole) of ethylethoxymethylenemalonate and 41.3 g (0.255 mole) of 3,5-dichloroanilinewere introduced into a stirred reactor provided with a distillationcolumn.

The mixture was heated from ambient temperature to 248° C. over 3 h 30minutes, then maintained at 248° C. for 3 h; the ethanol formed wasdistilled off as it was formed.

b—Hydrolysis—Decarboxylation of the ethyl4-hydroxy-5,7-dichloroquinoline-3-carboxylate obtained

The temperature of the reaction mixture obtained above was reduced to95° C. and 142.3 g of aqueous 25% potassium hydroxide solution (0.638moles) was added.

It was heated to 95° C.-100° C. for 9 hours then 28.6 g of aqueous 25%potassium hydroxide solution (0.128 moles) was added.

It was decanted at 85° C. for 2 hours than the aqueous potassiumhydroxide phase was separated from the Therminol VP1 phase.

This aqueous phase was acidified with 412 g of an aqueous 10.5%sulphuric acid solution (0.437 moles).

The precipitate obtained was filtered, washed with water and dried.

48.8 g of a product containing 66% of ODCQA and 33% of thedecarboxylated product DCHQ were obtained.

EXAMPLES 24 TO 26

In the following examples, sodium hydroxide was used in place ofpotassium hydroxide.

The conditions used and results obtained are shown in Table (IV).

TABLE (IV) NaOH/ODCQA [NaOH] TT RR Ref. mole mol/kg of Time ODCQA DCHQEx. ratio reaction medium Solvent T° C. h % % 24 1.19 0.7 None 140 785.5 85.5 25 1.60 1.05 None 140 7 90 89.8 26 2.05 1.35 None 140 7 9089.3

EXAMPLE 27

The following were charged into a 1.5 liter LIST discotherm B® reactor:

1 liter of water;

50.4 g of sodium bicarbonate (0.6 moles);

154.8 g of ODCQA (0.6 moles).

It was stirred at 30 rpm.

A suspension was obtained and gas evolution was observed.

The autoclave was closed and heated for 45 min to 120° C.: the pressurewas 4.87 bars.

It was degassed to 3 bars.

It was re-sealed and heated for 2 hours 15 minutes to 150° C.,decompressing from time to time (twice).

When the reaction was complete, the pressure was 686 bars.

It was cooled and the pressure was returned to atmospheric pressure.

A suspension was obtained which was diluted with 1 liter of water.

1920 g of suspension was recovered.

The suspension was filtered and 315 g of moist cake was obtained alongwith 1698 g of mother liquor.

After drying the moist cake, 138.6 g of dry product with the followingcomposition was obtained:

ODCG=98%;

ODCQA=0.83%

The base initially introduced was present in the mother liquor whichcould thus be recycled to a new decarboxylation step to prevent thedischarge of effluents.

What is claimed is:
 1. A process for the preparation of a4-hydroxyquinoline compound, or its tautomeric form, from a startingcompound having the following formula:

wherein: R₁, which is identical or different, represents a linear orbranched alkyl group containing 1 to 12 carbon atoms, a linear orbranched alkyl group containing 1 to 6 carbon atoms, carrying one ormore halogen atoms, a linear or branched alkenyl group containing 2 to12 carbon atoms, a cyclohexyl group, a phenyl group, a benzyl group, alinear or branched alkoxy or group containing 1 to 6 carbon atoms, alinear or branched thioether group containing 1 to 6 carbon atoms, anacyl group containing 2 to 6 carbon atoms, a nitro group, an aminogroup, optionally substituted by alkyl groups containing 1 to 6 carbonatoms, a halogen atom, a trifluoromethyl group, or an alkenylene groupcontaining 3 or 4 carbon atoms, optionally forming a ring with a carbonatom adjacent to a phenyl ring; Y represents a CN group, a COOR₂ group,or a CONR₃R₄ group, wherein groups R₂, R₃ or R₄, which are identical ordifferent, represent a hydrogen atom, an alkyl group, a cyclohexylgroup, a phenyl group, or a benzyl group; n is a number in the range 1to 4, said process comprising the steps of: a) heating said startingcompound to a temperature of at most 200° C. in the presence of a base,and b) recovering the compound obtained in step a).
 2. A processaccording to claim 1, wherein groups R₁, which are identical ordifferent, represent a chlorine atom, a methyl group, or a methoxygroup.
 3. A process according to claim 1, wherein groups R₂, R₃ and R₄,which are identical or different, represent a hydrogen atom or an alkylgroup containing 1 to 6 carbon atoms.
 4. A process according to claim 1,wherein the starting compound with formula (I) is in its tautomeric form(II):

wherein R₁, which is identical or different, represents a linear orbranched alkyl group containing 1 to 12 carbon atoms, a linear orbranched alkyl group containing 1 to 6 carbon atoms, carrying one ormore halogen atoms, a linear or branched alkenyl group containing 2 to12 carbon atoms, a cyclohexyl group, a phenyl group, a benzyl group, alinear or branched alkoxy or group containing 1 to 6 carbon atoms, alinear or branched thioether group containing 1 to 6 carbon atoms, anacyl group containing 2 to 6 carbon atoms, a nitro group, an aminogroup, optionally substituted by alkyl groups containing 1 to 6 carbonatoms, a halogen atom, a trifluoromethyl group, or an alkenylene groupcontaining 3 or 4 carbon atoms, optionally forming a ring with a carbonatom adjacent to a phenyl ring; Y represents a CN group, a COOR₂ group,or a CONR₃R₄ group, wherein groups R₂, R₃ or R₄, which are identical ordifferent, represent a hydrogen atom, an alkyl group, a cyclohexylgroup, a phenyl group, or a benzyl group; n is a number in the range 1to
 4. 5. A process according to claim 1, wherein the starting compoundis 4-hydroxy-7-chloroquinoline-3-carboxylic acid,4-hydroxy-5-chloroquinoline-3-carboxylic acid, or4-hydroxy-5,7-dichloroquinoline-3-carboxylic acid.
 6. A processaccording to claim 1, wherein the starting compound is4-hydroxy-5,7-dichloroquinoline-3-carboxylic acid, methyl4-hydroxy-5,7-dichloroquinoline-3-carboxylate, or ethyl4-hydroxy-5,7-dichloroquinoline-3-carboxylate.
 7. A process according toclaim 1, wherein the base is an alkaline base.
 8. A process according toclaim 7, wherein the base is an alkali metal hydroxide, an alkali metalbicarbonate or an alkali metal carbonate.
 9. A process according toclaim 7, wherein the mole ratio between the number of moles of base, orequivalents of base, and the number of moles of the starting compound isin the range 1 to
 6. 10. A process according to claim 7, wherein themole ratio between the number of moles of base, or equivalents of base,and the number of moles of the starting compound is in the range 1.5 to3.5.
 11. A process according to claim 1, wherein step a) essentiallyconsists in a decarboxylation reaction carried out in the presence ofwater in liquid or vapor form.
 12. A process according to claim 11,wherein the quantity of starting compound represents 2% to 50% by weightof the water.
 13. A process according to claim 11, wherein the quantityof starting compound represents 5% to 35% by weight of the water.
 14. Aprocess according to claim 1, wherein in step a) the temperature isbetween 90° C. and 190° C.
 15. A process according to claim 1, whereinin step a) the temperature is between 95° C. and 180° C.
 16. A processaccording to claim 11, wherein the decarboxylation reaction is carriedout by heating a reaction mixture comprising the starting compound, thebase and water.
 17. A process according to claim 11, further comprising,before step a), the steps of mixing in an aqueous solution the startingcompound and the base, and evaporating off the water, thedecarboxylation being carried out by heating in a solely solid medium.18. A process according claim 11, wherein the decarboxylation reactionis carried out in the presence of an organic solvent.
 19. A processaccording to claim 18, wherein the organic solvent is a paraffin oil, aneutectic mixture of biphenyl oxide and biphenyl, a triphenylmethane, asulpholane, a benzylbenzene, a 1,4-dibenzylbenzene, a silicone oil, apetroleum cut with a high boiling point, a dimethylformamide, aN,N′-diacetamide, or an alcohol.
 20. A process according to claim 18,wherein the concentration of the starting compound in the organicsolvent is such that the organic solvent and the starting compoundpresent a weight ratio solvent/starting compound of between 1 and 10.21. A process according to claim 18, wherein the concentration of thestarting compound in the organic solvent is such that the organicsolvent and the starting compound present a weight ratiosolvent/starting compound of between 1 and
 10. 22. A process accordingto claim 1, wherein recovering in step b) is carried out by asolid/liquid separation, optionally after an acidic treatment.